A cilia-independent function of BBSome mediated by DLK-MAPK signaling in C. elegans photosensation.
Dev Cell
; 57(12): 1545-1557.e4, 2022 06 20.
Article
em En
| MEDLINE
| ID: mdl-35649417
ABSTRACT
Bardet-Biedl syndrome (BBS) is a genetic disorder that affects primary cilia. BBSome, a protein complex composed of eight BBS proteins, regulates the structure and function of cilia, and its malfunction causes BBS in humans. Here, we report a cilia-independent function of BBSome. To identify genes that regulate the C. elegans photoreceptor protein LITE-1 in ciliated ASH photosensory neurons, we performed a genetic screen and isolated bbs mutants. Functional analysis revealed that BBSome regulates LITE-1 protein stability independently of cilia. Through another round of genetic screening, we found that this cilia-independent function of BBSome is mediated by DLK-MAPK signaling, which acts downstream of BBSome to control LITE-1 stability via Rab5-mediated endocytosis. BBSome exerts its function by regulating the expression of DLK. BBSome also regulates the expression of LZK, a mammalian DLK in human cells. These studies identify a cilia-independent function of BBSome and uncover DLK as an evolutionarily conserved BBSome effector.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Cílios
/
Síndrome de Bardet-Biedl
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Dev Cell
Ano de publicação:
2022
Tipo de documento:
Article